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Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
Rasa, S, Nora-Krukle, Z, Henning, N, Eliassen, E, Shikova, E, Harrer, T, Scheibenbogen, C, Murovska, M, Prusty, BK
Journal of translational medicine. 2018;16(1):268
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The causes of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are currently unknown, however viruses have been implicated. The absence of well-designed studies has hindered the understanding of this disease and the aim of this review was to discuss the literature regarding viruses and ME/CFS. Several viruses were discussed including the herpes virus, which is responsible for illnesses such as chicken pox and cold sores. This virus has not always been associated with the onset of ME/CFS, however it may be in certain individuals. The enteroviruses, which are responsible for illnesses such as hand, foot and mouth and polio, were also reviewed and it was concluded that it is unlikely that these have a role in ME/CFS. Several other viruses were also discussed. The authors then went on to describe how these viruses can affect human cells, potentially causing ME/CFS. It was concluded that the data available is controversial and only certain individuals may be affected, better studies are required. This study could be used by healthcare professionals to identify individuals at risk of ME/CFS following viral infection and understanding how ME/CFS may develop.
Abstract
BACKGROUND AND MAIN TEXT Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and controversial clinical condition without having established causative factors. Increasing numbers of cases during past decade have created awareness among patients as well as healthcare professionals. Chronic viral infection as a cause of ME/CFS has long been debated. However, lack of large studies involving well-designed patient groups and validated experimental set ups have hindered our knowledge about this disease. Moreover, recent developments regarding molecular mechanism of pathogenesis of various infectious agents cast doubts over validity of several of the past studies. CONCLUSIONS This review aims to compile all the studies done so far to investigate various viral agents that could be associated with ME/CFS. Furthermore, we suggest strategies to better design future studies on the role of viral infections in ME/CFS.
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Antidepressant utilisation and incidence of weight gain during 10 years' follow-up: population based cohort study.
Gafoor, R, Booth, HP, Gulliford, MC
BMJ (Clinical research ed.). 2018;361:k1951
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Obesity is an increasing concern worldwide and the USA and UK have some of the highest rates of obesity in the world. Anti-depressant medications are also increasing prescribed, and there is an established association between obesity and depression. These medications may also contribute to weight gain, although the mechanisms for this are not clearly understood. This large UK-population based cohort study aimed to evaluate the long term association between anti-depressant prescriptions and body weight, using data from the UK Clinical Practice Research Datalink from 2004-2014. Weight gain of >=5% was measured. The number of incidences of >=5% weight gain was significantly higher for patients prescribed an anti-depressant than those who were not, after adjusting for confounding factors such as age, smoking status, social status, comorbidity and co-prescribing. This was particularly so during the 2nd and 3rd year of treatment, when there was a 46% higher risk of >=5% weight gain compared to the general population. It was also found that some anti-depressants contributed to higher weight gain than others. Whilst the associations may not be causal, the potential for weight gain should be considered when anti-depressant medications are indicated.
Abstract
OBJECTIVE To evaluate the long term association between antidepressant prescribing and body weight. DESIGN Population based cohort study. SETTING General practices contributing to the UK Clinical Practice Research Datalink, 2004-14. PARTICIPANTS 136 762 men and 157 957 women with three or more records for body mass index (BMI). MAIN OUTCOME MEASURES The main outcomes were antidepressant prescribing, incidence of ≥5% increase in body weight, and transition to overweight or obesity. Adjusted rate ratios were estimated from a Poisson model adjusting for age, sex, depression recording, comorbidity, coprescribing of antiepileptics or antipsychotics, deprivation, smoking, and advice on diet. RESULTS In the year of study entry, 17 803 (13.0%) men and 35 307 (22.4%) women with a mean age of 51.5 years (SD 16.6 years) were prescribed antidepressants. During 1 836 452 person years of follow-up, the incidence of new episodes of ≥5 weight gain in participants not prescribed antidepressants was 8.1 per 100 person years and in participants prescribed antidepressants was 11.2 per 100 person years (adjusted rate ratio 1.21, 95% confidence interval 1.19 to 1.22, P<0.001). The risk of weight gain remained increased during at least six years of follow-up. In the second year of treatment the number of participants treated with antidepressants for one year for one additional episode of ≥5% weight gain was 27 (95% confidence interval 25 to 29). In people who were initially of normal weight, the adjusted rate ratio for transition to overweight or obesity was 1.29 (1.25 to 1.34); in people who were initially overweight, the adjusted rate ratio for transition to obesity was 1.29 (1.25 to 1.33). Associations may not be causal, and residual confounding might contribute to overestimation of associations. CONCLUSION Widespread utilisation of antidepressants may be contributing to long term increased risk of weight gain at population level. The potential for weight gain should be considered when antidepressant treatment is indicated.
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Orthorexia nervosa: A behavioral complex or a psychological condition?
Strahler, J, Hermann, A, Walter, B, Stark, R
Journal of behavioral addictions. 2018;7(4):1143-1156
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Orthorexia nervosa (ON) is a condition characterised by an obsession for 'healthy eating' and avoidance of 'unhealthy food' with the violation of these rigid dietary rules being associated with shame, anxiety and distress. Whilst numerous studies have evidenced its existence, there is debate as to whether it is a behavioural phenomenon or a mental health condition like other eating disorders. Anecdotally, there are reports of physiological impacts (such as weight loss), psychological impacts (such as emotional instability) and social impacts (such as social isolation), which are similar to clinical eating disorders. This cross-sectional study aimed to explore whether ON is of clinical relevance, and if it can be distinguished from other mental health conditions. An online survey including orthorexic behaviours was completed by 713 subjects (80% female) aged 18-75 years. 4% showed significant orthorexic eating alongside lower levels of life satisfaction, wellbeing and higher levels of stress. Depression and obsessive compulsive tendencies were also found in 48% and 30% of those with ON respectively. The authors conclude that there are strong overlaps between ON, mental health conditions and disturbed eating behaviours, questioning whether it should be a mental health condition in its own right.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Orthorexia nervosa has been associated with other mental health conditions, including depression and obsessive compulsive disorder.
- Given this association, and the desire for individuals with the condition to seek validation of their orthorexic eating, healthcare practitioners should make appropriate referral to ensure the safety and wellbeing of these individuals.
- Debate continues on whether orthorexia nervosa should be viewed as a mental health condition and eating disorder or a behavioural phenomenon.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Orthorexia nervosa (ON) is gaining increasing interest in research and clinical practice. Whilst research has evidenced its existence, there is still an active debate of whether it should be viewed as a mental health condition and eating disorder in its own right. Diagnoses may be useful for some individuals to make sense of the symptoms they are experiencing, reduce their feelings of isolation and to help them take steps to get the right support needed to improve their health. In a similar way to other eating disorders, orthorexia nervosa has been associated with other mental health conditions including depression and obsessive compulsive disorder.
Clinical practice applications:
Whether defined as an eating disorder in its own right or not, orthorexia nervosa nevertheless is likely to have an impact on wellbeing, life satisfaction and stress. It is an important condition or behavioural phenomenon for practitioners to be aware of, particularly in nutrition fields that may attract those individuals looking for more information or endorsement of their desired orthorexic eating. Given its association with other mental health conditions, safety and appropriate referral should be made to ensure the wellbeing of these individuals.
Considerations for future research:
Research on orthorexia nervosa is considerably smaller compared to other eating disorder conditions and behaviours. Further empirical evidence is needed to support the debate as to whether it is an eating disorder in its own right, or a behavioural phenomenon, and further insight needed to establish its full impact on physical and psychological health.
Abstract
BACKGROUND AND AIMS Numerous studies have provided evidence for orthorexia nervosa (ON), an eating pattern characterized by an almost manic obsession for and fixation on healthy eating, to be of epidemiological relevance. However, there is scientific debate on whether it is merely a behavioral or lifestyle phenomenon as compared to a mental disorder. Aim of this cross-sectional study was to explore whether ON is of epidemiological and clinical relevance, and whether ON can be distinguished from other mental health disorders and healthy lifestyle features. METHODS An online survey including a measure of orthorexic behaviors [Duesseldorf Orthorexia Scale (DOS)], well-being and distress, eating behaviors, pathological eating, anxiety and depression, addictive behaviors, obsessive-compulsive symptoms, personality, and health behaviors was completed by 713 subjects (79.8% women, 18-75 years, median age: 25 years). RESULTS Twenty-seven subjects (3.8%, 21 women) showed significant orthorexic eating (DOS ≥ 30). ON cases reported lower well-being, lower satisfaction with life, and higher current stress levels than non-ON cases. The highest percentage of variation in ON was explained by pathological eating (R2 = .380), followed by eating style, Mediterranean diet, compulsive symptoms, and subjective social status. Importantly, ON provided hardly any additional predictive value for well-being when also considering pathological eating. DISCUSSION AND CONCLUSIONS Our data confirmed the epidemiological and clinical relevance of orthorexic behaviors, but the strong conceptual overlap with other mental health problems and pathological eating raise initial doubts as to whether ON is a distinct mental health disorder category. This co-occurrence, unique symptoms, and underlying processes need further exploration by comparing ON cases with patients with other mental disorders.
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A sympathetic nervous system evaluation of obesity stigma.
Oliver, MD, Datta, S, Baldwin, DR
PloS one. 2017;12(10):e0185703
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The negative health consequences of obesity are well known. Those classified as obese also suffer from discrimination which has further negative psychological and physiological effects on well-being. The aim of this study was to see if attitudes to obesity can be modified at the physiological and psychological level by priming. 70 people aged 18-53 were randomly assigned to 2 groups. One group was shown images of obesity in negative settings, the other in positive settings. All participants then viewed an actual obesity discrimination incident. Levels of the digestive enzyme salivary alpha amylase (sAA) and skin conductance (SC) were taken as measures of sympathetic nervous system (SNS) activity. Individuals in the negative priming group had significantly more SC arousal and exhibited the highest overall sAA response after viewing the incident when compared to the positively primed group. The authors conclude that clinicians addressing stigma issues should consider the use of positively primed images as a method for reducing the possible long-term physiological consequences of the negative attitudes surrounding obesity.
Abstract
The portrayal of obesity in the media is often one of negativity. Consequently, it may generate an increase in stigma. Obesity stigma, a form of social discrimination, is responsible for many of the negative psychological and physiological effects on individual wellness. These effects not only impact individual health, but also affect the economy, and ultimately, societal wellness. In an attempt to examine the influence of the media on obesity stigma, this study tested the hypothesis that positive priming would lead to a reduction in obesity stigma. To further our understanding of this relationship, we: 1) examined the role of priming on physiological measures (e.g. salivary alpha amylase and skin conductance) in 70 college students by introducing positive and negative media images of individuals with obesity, and 2) assessed psychological measures (e.g. perceived stress, need to belong, and self-esteem, and Body Mass Index). After the priming manipulation, participants read a vignette depicting the discrimination of an individual with obesity and answered subsequent questions assessing participants' attributional blame of obesity. Results of this study revealed that priming affects physiological responding to obesity stigmatization. In conclusion, these findings suggest that incorporating positive media images of individuals with obesity may be an effective tool for reducing stigma and the various physiological consequences associated with it, which in turn, can enhance societal health and wellness.
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Gut microbiome alterations in Alzheimer's disease.
Vogt, NM, Kerby, RL, Dill-McFarland, KA, Harding, SJ, Merluzzi, AP, Johnson, SC, Carlsson, CM, Asthana, S, Zetterberg, H, Blennow, K, et al
Scientific reports. 2017;7(1):13537
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Research into what causes Alzheimer’s Disease (AD) is on-going, including a proposal for a potential role of human bacterial profiles. This cross-sectional study of 25 patients diagnosed with AD and 25 individuals with no AD diagnosis (matched for age, sex, ethnicity, BMI and diabetes status) aimed to compare the gut microbiome between AD and non-AD states using faecal samples. The researchers found that the gut microbiome of the AD patients was less diverse and compositionally distinct from the age-matched control group. In particular, the AD group had decreased Firmicutes and Bifidobacterium and increased Bacteriodetes compared with control. This small study suggests therefore that the gut microbiome may be a target for therapeutic manipulation when working with patients with AD.
Abstract
Alzheimer's disease (AD) is the most common form of dementia. However, the etiopathogenesis of this devastating disease is not fully understood. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition, yet the microbial communities associated with AD have not been characterized in humans. Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals. We identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. Furthermore, we observed correlations between levels of differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD. These findings add AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.
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A double-blind, randomized, comparative study of the use of a combination of uridine triphosphate trisodium, cytidine monophosphate disodium, and hydroxocobalamin, versus isolated treatment with hydroxocobalamin, in patients presenting with compressive neuralgias.
Goldberg, H, Mibielli, MA, Nunes, CP, Goldberg, SW, Buchman, L, Mezitis, SG, Rzetelna, H, Oliveira, L, Geller, M, Wajnsztajn, F
Journal of pain research. 2017;10:397-404
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Uridine and cytidine are nucleotides, which play several fundamental roles in cellular metabolism, including being components of DNA, energy transfer, intracellular signalling and neurotransmission. Vitamin B12 is essential for growth and maintenance of a variety of processes, including synthesis of myelin (an important structure of the nervous system) and nerve metabolism. The objectives of this randomised, double-blind, comparative, controlled clinical trial were to assess the safety and efficacy of the combination of nucleotides (uridine triphosphate, UTP and cytidine monophosphate, CMP) and vitamin B12 in patients presenting with pain due to neural compression, compared with vitamin B12 on its own. Patients received 15mg CMP, 9mg UTP and 6mg vitamin B12 or 6mg vitamin B12 only, for 30 days and were assessed before start and at 15 and 30 days of treatment. Outcome measures included a visual analog pain scale (VAS), and the Patient Functionality Questionnaire (PFQ), as well as adverse effects, including changes in blood parameters. 191 patients in each group completed the trial. Both groups showed statistically significant improvements at the end of the study in relation to pre-treatment PFQ and VAS scores, but improvements were statistically better in the combination therapy compared to vitamin B12 alone. Adverse events were reported in both treatment groups, but these were transient and no severe adverse event occurred during the study period. The authors conclude that the combination of uridine, cytidine, and vitamin B12 was effective in the treatment of neuropathic pain and that further, larger studies are warranted.
Abstract
CONTEXT This paper reports on the results of treatment of compressive neuralgia using a combination of nucleotides (uridine triphosphate trisodium [UTP] and cytidine monophosphate disodium [CMP]) and vitamin B12. OBJECTIVES To assess the safety and efficacy of the combination of nucleotides (UTP and CMP) and vitamin B12 in patients presenting with neuralgia arising from neural compression associated with degenerative orthopedic alterations and trauma, and to compare these effects with isolated administration of vitamin B12. METHODS A randomized, double-blind, controlled trial, consisting of a 30-day oral treatment period: Group A (n=200) receiving nucleotides + vitamin B12, and Group B (n=200) receiving vitamin B12 alone. The primary study endpoint was the percentage of subjects presenting pain visual analog scale (VAS) scores ≤20 at end of study treatment period. Secondary study endpoints included the percentage of subjects presenting improvement ≥5 points on the patient functionality questionnaire (PFQ); percentage of subjects presenting pain reduction (reduction in VAS scores at study end in relation to pretreatment); and number of subjects presenting adverse events. RESULTS The results of this study showed a more expressive improvement in efficacy evaluations among subjects treated with the combination of nucleotides + vitamin B12, with a statistically significant superiority of the combination in pain reduction (evidenced by VAS scores). There were adverse events in both treatment groups, but these were transitory and no severe adverse event was recorded during the study period. Safety parameters were maintained throughout the study in both treatment groups. CONCLUSION The combination of uridine, cytidine, and vitamin B12 was safe and effective in the treatment of neuralgias arising from neural compression associated with degenerative orthopedic alterations and trauma.
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Therapist-supported Internet cognitive behavioural therapy for anxiety disorders in adults.
Olthuis, JV, Watt, MC, Bailey, K, Hayden, JA, Stewart, SH
The Cochrane database of systematic reviews. 2016;3:CD011565
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Previous research has supported the use of cognitive behavioural therapy (CBT) in the treatment of anxiety disorders, which is aimed at changing negative or unhealthy thinking patterns. Many individuals with anxiety find it challenging to get to CBT appointments and so an internet-based programme, with telephone and email support, has been developed. This systematic review of 38 randomised controlled trial studies aimed to assess the effects of internet CBT (ICBT) on anxiety symptoms and severity. The results showed that there was a clinically important improvement in anxiety alongside reductions in symptom severity and an increase in the patient’s quality of life (QoL) when following ICBT compared to no treatment or online support group discussions. When comparing supported ICBT and self-guided CBT there were no differences between anxiety symptom severity and QoL. When comparing ICBT and face to face therapist-supported CBT, no differences were reported in anxiety symptoms and QoL. It was concluded that ICBT is more beneficial than no treatment or online discussion groups and may be just as useful as face-to-face CBT. The number of studies that compared ICBT to self-guided CBT was limited and so specific conclusions were difficult to ascertain. This study could be used by healthcare professionals to understand that people suffering from anxiety may not be receiving the treatment they need for fears of new situations or leaving the house. In this instance ICBT is an alternative treatment that is just as beneficial as face-to-face therapy.
Abstract
BACKGROUND Cognitive behavioural therapy (CBT) is an evidence-based treatment for anxiety disorders. Many people have difficulty accessing treatment, due to a variety of obstacles. Researchers have therefore explored the possibility of using the Internet to deliver CBT; it is important to ensure the decision to promote such treatment is grounded in high quality evidence. OBJECTIVES To assess the effects of therapist-supported Internet CBT (ICBT) on remission of anxiety disorder diagnosis and reduction of anxiety symptoms in adults as compared to waiting list control, unguided CBT, or face-to-face CBT. Effects of treatment on quality of life and patient satisfaction with the intervention were also assessed. SEARCH METHODS We searched the Cochrane Depression, Anxiety and Neurosis Review Group Specialised Register (CCDANCTR) to 16 March 2015. The CCDANCTR includes relevant randomised controlled trials from MEDLINE, EMBASE, PsycINFO and CENTRAL. We also searched online clinical trial registries and reference lists of included studies. We contacted authors to locate additional trials. SELECTION CRITERIA Each identified study was independently assessed for inclusion by two authors. To be included, studies had to be randomised controlled trials of therapist-supported ICBT compared to a waiting list, attention, information, or online discussion group; unguided CBT (that is, self-help); or face-to-face CBT. We included studies that treated adults with an anxiety disorder (panic disorder, agoraphobia, social phobia, post-traumatic stress disorder, acute stress disorder, generalized anxiety disorder, obsessive compulsive disorder, and specific phobia) defined according to the Diagnostic and Statistical Manual of Mental Disorders III, III-R, IV, IV-TR or the International Classification of Disesases 9 or 10. DATA COLLECTION AND ANALYSIS Two authors independently assessed the risk of bias of included studies and judged overall study quality. We used data from intention-to-treat analyses wherever possible. We assessed treatment effect for the dichotomous outcome of clinically important improvement in anxiety using a risk ratio (RR) with 95% confidence interval (CI). For disorder-specific and general anxiety symptom measures and quality of life we assessed continuous scores using standardized mean differences (SMD). We examined statistical heterogeneity using the I(2) statistic. MAIN RESULTS We screened 1736 citations and selected 38 studies (3214 participants) for inclusion. The studies examined social phobia (11 trials), panic disorder with or without agoraphobia (8 trials), generalized anxiety disorder (5 trials), post-traumatic stress disorder (2 trials), obsessive compulsive disorder (2 trials), and specific phobia (2 trials). Eight remaining studies included a range of anxiety disorder diagnoses. Studies were conducted in Sweden (18 trials), Australia (14 trials), Switzerland (3 trials), the Netherlands (2 trials), and the USA (1 trial) and investigated a variety of ICBT protocols. Three primary comparisons were identified, therapist-supported ICBT versus waiting list control, therapist-supported versus unguided ICBT, and therapist-supported ICBT versus face-to-face CBT.Low quality evidence from 11 studies (866 participants) contributed to a pooled risk ratio (RR) of 3.75 (95% CI 2.51 to 5.60; I(2) = 50%) for clinically important improvement in anxiety at post-treatment, favouring therapist-supported ICBT over a waiting list, attention, information, or online discussion group only. The SMD for disorder-specific symptoms at post-treatment (28 studies, 2147 participants; SMD -1.06, 95% CI -1.29 to -0.82; I(2) = 83%) and general anxiety symptoms at post-treatment (19 studies, 1496 participants; SMD -0.75, 95% CI -0.98 to -0.52; I(2) = 78%) favoured therapist-supported ICBT; the quality of the evidence for both outcomes was low.One study compared unguided CBT to therapist-supported ICBT for clinically important improvement in anxiety at post-treatment, showing no difference in outcome between treatments (54 participants; very low quality evidence). At post-treatment there were no clear differences between unguided CBT and therapist-supported ICBT for disorder-specific anxiety symptoms (5 studies, 312 participants; SMD -0.22, 95% CI -0.56 to 0.13; I(2) = 58%; very low quality evidence) or general anxiety symptoms (2 studies, 138 participants; SMD 0.28, 95% CI -2.21 to 2.78; I(2) = 0%; very low quality evidence).Compared to face-to-face CBT, therapist-supported ICBT showed no significant differences in clinically important improvement in anxiety at post-treatment (4 studies, 365 participants; RR 1.09, 95% CI 0.89 to 1.34; I(2) = 0%; low quality evidence). There were also no clear differences between face-to-face and therapist supported ICBT for disorder-specific anxiety symptoms at post-treatment (7 studies, 450 participants; SMD 0.06, 95% CI -0.25 to 0.37; I(2) = 60%; low quality evidence) or general anxiety symptoms at post-treatment (5 studies, 317 participants; SMD 0.17, 95% CI -0.35 to 0.69; I(2) = 78%; low quality evidence).Overall, risk of bias in included studies was low or unclear for most domains. However, due to the nature of psychosocial intervention trials, blinding of participants and personnel, and outcome assessment tended to have a high risk of bias. Heterogeneity across a number of the meta-analyses was substantial, some was explained by type of anxiety disorder or may be meta-analytic measurement artefact due to combining many assessment measures. Adverse events were rarely reported. AUTHORS' CONCLUSIONS Therapist-supported ICBT appears to be an efficacious treatment for anxiety in adults. The evidence comparing therapist-supported ICBT to waiting list, attention, information, or online discussion group only control was low to moderate quality, the evidence comparing therapist-supported ICBT to unguided ICBT was very low quality, and comparisons of therapist-supported ICBT to face-to-face CBT were low quality. Further research is needed to better define and measure any potential harms resulting from treatment. These findings suggest that therapist-supported ICBT is more efficacious than a waiting list, attention, information, or online discussion group only control, and that there may not be a significant difference in outcome between unguided CBT and therapist-supported ICBT; however, this latter finding must be interpreted with caution due to imprecision. The evidence suggests that therapist-supported ICBT may not be significantly different from face-to-face CBT in reducing anxiety. Future research should explore heterogeneity among studies which is reducing the quality of the evidence body, involve equivalence trials comparing ICBT and face-to-face CBT, examine the importance of the role of the therapist in ICBT, and include effectiveness trials of ICBT in real-world settings. A timely update to this review is needed given the fast pace of this area of research.